The influence of behavioral conditioning on the development of tolerance to ethanol will be examined. A paradigm will be developed in which tolerance to ethanol can be observed only with the appropriately conditioned cues, a compensatory response would be expected when a placebo injection would be given under the circumstances in which the animal has learned to expect ethanol, and the tolerance to ethanol would be expected to be diminished by an extinction procedure. The mechanism underlying tolerance produced by behavioral conditioning will be investigated in several ways. The possible involvement of metabolic or dispositional factors will be assessed by determining blood and brain levels of ethanol following injections given to conditioned animals in appropriate circumstances and to control animals. Using hypothermia as the measure of drug effect, cross-tolerance to agonists of different central neurotransmitter systems will be tested. Tolerance produced by a conditioning method will be compared to tolerance produced by a more pharmacological technique, i.e., presenting the animals with a liquid diet containing ethanol. Animals rendered tolerant to ethanol by the dietary technique will also be tested for their response to 1 a placebo injection; 2 an extinction procedure; and 3 tests for cross-tolerance to agonists of different central neurotransmitter systems. A conditioning paradigm will be developed for each of the hypothermic agents so that cross-tolerance to ethanol can be tested.